Effectiveness and safety of anlotinib plus anti-programmed cell death 1/ligand 1 (anti-PD-1/PD-L1) antibodies as maintenance therapy after first-line chemotherapy combined with anti-PD-1/PD-L1 antibodies in extensive-stage small cell lung cancer: a real-world study.

Background: Currently, chemotherapy plus immunotherapy followed by maintenance therapy with immune monotherapy is the preferred first-line treatment option for extensive-stage small cell lung cancer (ES-SCLC), but with limited overall survival (OS) and progression-free survival (PFS) benefits. The combination of anti-angiogenic drugs with immunotherapy has shown encouraging anti-tumor activity and tolerability, with some degree of overcoming immune resistance. This study aimed to evaluate the effectiveness and safety of anlotinib plus anti-programmed cell death 1/ligand 1 (anti-PD-1/PD-L1) antibodies as maintenance therapy after first-line chemotherapy combined with immunotherapy in ES-SCLC. Methods: Between June 2020 and December 2021, 12 patients with newly diagnosed ES-SCLC in the First Affiliated Hospital of Army Medical University were retrospectively analyzed. All patients without disease progression after 4-6 cycles of first-line platinum-containing chemotherapy plus anti-PD-1/PD-L1 antibodies received anlotinib (12 mg oral/day, days 1-14, followed by 1 week off, every 3 weeks per cycle) plus anti-PD-1/PD-L1 antibodies as maintenance therapy. Several patients underwent chest radiotherapy (intensity-modulated radiotherapy using a 6 MV X-ray) without disease progression before maintenance therapy. The effectiveness and safety of anlotinib plus anti-PD-1/PD-L1 antibodies as maintenance therapy after first-line chemotherapy combined with immunotherapy in ES-SCLC were evaluated. Results: The median follow-up time was 31.1 months. During first-line treatment (including maintenance therapy), one patient achieved a complete response, eight patients achieved a partial response (PR), and three patients had stable disease, with an objective response rate of 75.0% and a disease control rate of 100.0%. During maintenance therapy with anlotinib plus anti-PD-1/PD-L1 antibodies, 50.0% of patients achieved further lesion remission on the basis of the prior initial treatment, of which one patient achieved a PR. The median PFS was 13.6 [95% confidence interval (CI): 11.2-15.6] months, and the median OS was 19.5 (95% CI: 14.5-24.5) months. Treatment-related any grade and grade 3-4 adverse events (AEs) were reported in 100.0% and 58.3% of patients, respectively. No life-threatening AEs were observed. Grade 3-4 AEs included leukocytopenia (58.3%, 7/12), thrombocytopenia (33.3%, 4/12), nausea (33.3%, 4/12), anemia (16.7%, 2/12), and fatigue (8.3%, 1/12). All AEs during maintenance therapy were tolerated and were regarded as grade 1-2, with the majority being fatigue, nausea, rash, and hemoptysis. Conclusions: The combination of anlotinib with anti-PD-1/PD-L1 antibodies demonstrated encouraging effectiveness and safety in treating patients with ES-SCLC, suggesting that it may be a preferred option for maintenance therapy after first-line chemotherapy combined with immunotherapy.